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Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

The growing use of imaging examinations has led to increased detection of spontaneous coronary artery dissection (SCAD) as a non-atherosclerotic cause of acute coronary syndrome (ACS). Since a greater awareness of pathophysiologic mechanisms has relevant implications in clinical practice, we aim to provide an update to current knowledge of SCAD pathophysiology. We discuss the most common conditions associated with SCAD, including predisposing factors and triggers, and focus on potential mechanisms leading to SCAD development. Furthermore, we report the main genetic research findings that have shed further light on SCAD pathophysiology. Finally, we summarize practical considerations in SCAD management based on pathophysiologic insights.

The incidence of atrial fibrillation (AF) is progressively increasing, in line with the aging of the population and with the increase in chronic diseases. The care burden of the disease and above all to its consequences (i.e. ischaemic stroke and heart failure) significantly impacts the various health systems with forecasts of exponential increase in the near future. Clinical forms of AF, i.e. those diagnosed with electrocardiogram, have a clear correlation with systemic embolic events and also with a reduction in survival. Thromboembolic prophylaxis in these patients, with anticoagulant drugs, has in fact been shown to greatly reduce the incidence of ischaemic stroke and improve survival. In recent decades, the widespread use of therapeutic intra-cardiac devices, which allow constant and continuous monitoring of myocardial electrical activity, is bringing to light a large number of atrial high rate episodes (AHREs), which are not associated with clinical manifestation. The incidence of these findings grows linearly with the duration of the observation. More independent studies have shown that AHREs are associated with a risk of stroke that is higher (about double) than controls but significantly lower than in patients with manifest AF. However, taking into consideration patients with ischaemic stroke and wearers of implantable devices, no temporal correlation emerged between the incidence of the ischaemic episode and arrhythmia. The presence of AHRE is associated with an approximately six-fold increase in the incidence of clinical AF but only a minority of these patients meet the criteria for prescribing anticoagulation. Pending the publication of the studies still in progress, the European Society of Cardiology guidelines for the treatment of AF recommend considering the initiation of anticoagulant therapy in patients with long-lasting AHRE (> 24 h) associated with a high embolic risk. In patients with episodes of shorter duration (1–24 h), especially if with high burden, anticoagulant therapy can be considered in case of very high embolic risk (e.g. secondary prevention, CHADVASc ≥ 3).

Patients with atrial fibrillation (AF) and chronic renal failure (CRF) represent a growing population in epidemiological terms since both conditions increase with advancing age. The association of AF and CRF is burdened with a poor prognosis and with a high risk of adverse events, both ischaemic and haemorrhagic. Oral anticoagulant therapy, in these patients, is more problematic, especially due to the concomitant increased risk of bleeding. The use of direct oral anticoagulants (DOACs) in patients with non-severe renal insufficiency appears to be safe and effective. Since all currently available DOACs are at least partially eliminated by the kidney (dabigatran is the direct anticoagulant with the highest rate of renal elimination, approximately 80%), periodic monitoring of renal function is recommended to evaluate possible need for dosage adjustment. In patients with advanced renal insufficiency, the use of DOAC appears controversial, given the small number of clinical studies that have tested its efficacy and safety. It is known, however, that oral anticoagulation therapy with vitamin K antagonists (VKAs) is associated with an increase in nephropathy and renal-vascular calcification. From this point of view, therapy with DOAC could be more advantageous than VKAs. Data from clinical studies would seem to show that the use of dabigatran and rivaroxaban in these patients may lead to a reduction in the inevitable deterioration of renal function.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

The number of elderly patients admitted to cardiac intensive care units (CICU) is significantly increasing. Nowadays, novel diagnostic and therapeutic tools allow to treat the vast majority of cardiac acute diseases, nonetheless care of elderly patients requires a careful clinical evaluation. A favorable proportion of cost-effectiveness is warranted, aimed at avoiding futile procedures or treatments. On the other hand, the availability of minimally invasive procedures carries forward old limits to treatments in elderly patients in CICU. It appears evident that age cannot per se represent a limit in the care of elderly people. The present review gives insights in the management of the most common cardiovascular disease settings in elderly patients in the CICUs, thus providing important tools in complex decision-making.

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through hepatic CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The FDA and the EMA sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like vitamin K antagonists (VKAs), DOACs can determine gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GI bleeding as compared with apixaban and warfarin. In patients taking oral anticoagulant with GI risk factor, PPI could be recommended, even if usefulness of PPIs in these patients deserves further data. Helicobacter pylori should always be searched, and treated, in patients with history of peptic ulcer disease (with or without complication). Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Background: The itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice. Hypothesis: The safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines. Methods: Adults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two-thirds of the enrollment period are presented. Results: A total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor. Conclusions: The interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

We would like to thank the authors of this letter for their comments [...]

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand antithrombotic therapy should reduce the risk related to recurrent ischemic events and/or stent thrombosis, on the other hand care should be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Mitral regurgitation (MR) is, by occurrence, the second most common valvular heart disease in the Western world, with a significant impact on prognosis and mortality. A significant number of patients with significant mitral incompetence cannot be submitted to conventional surgery due to high surgical risk. The need for an adequate therapeutical strategy prompted the development of innovative endovascular techniques. Among them, the MitraClip percutaneous system, mimicking the ‘edge-to-edge’ surgical technique introduced by Alfieri in 2003 has emerged as the treatment of choice in patients not suitable for conventional surgery. Since its introduction, this procedure has been effectively carried out in more than 35 000 patients. The evidences from the first randomized clinical trial, EVEREST II, suggested that the MitraClip system is effective in improving survival and quality of life in patients with severe MR. Further randomized trials, MITRA-FR and COAPT, added some more information, showing that an appropriate patient selection, close attention to the specific anatomical characteristics of the mitral valve, and adequate experience of the centre providing the treatment, are important determinants of the outcome of the procedure.

Background Although oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined. Objective to compare downstream and upstream oral P2Y12 inhibitors administration strategies in NSTE-ACS patients undergoing invasive management. Methods We performed a randomized, adaptive, open-label, multi-center, clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit). Results We randomized 1449 patients to downstream or upstream oral P2Y12 inhibitor administration. A prespecified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment). Conclusions Downstream and upstream oral P2Y12 inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)]

AIMS Clinical management of patients more than 1 year after acute myocardial infarction (MI) is challenging. Patient risk stratification may help to establish therapeutic priorities. We aimed to describe the comprehensive risk profile and management of patients with prior MI. METHODS We analyzed data from the EYESHOT Post-MI study, which evaluated the management of patients 1-3 years after MI. The risk profile of participants was defined according to the qualifying high-risk features of the PEGASUS-TIMI 54 trial (history of diabetes, history of recurrent MI, angiographic evidence of multivessel coronary disease, chronic kidney disease with estimated glomerular filtration rate

Objective The aim of the study is to describe the real-world use of the P2Y12 inhibitor cangrelor as a bridging strategy in patients at high thrombotic risk after percutaneous coronary intervention (PCI) and referred to surgery requiring perioperative withdrawal of dual antiplatelet therapy (DAPT). Materials and Methods We collected data from nine Italian centers on patients with previous PCI who were still on DAPT and undergoing nondeferrable surgery requiring DAPT discontinuation. A perioperative standardized bridging protocol with cangrelor was used. Results Between December 2017 and April 2019, 24 patients (mean age 72 years; male 79%) were enrolled. All patients were at high thrombotic risk after PCI and required nondeferrable intermediate to high bleeding risk surgery requiring DAPT discontinuation (4.6 ± 1.7 days). Cangrelor infusion was started at a bridging dose (0.75 µg/kg/min) 3 days before planned surgery and was discontinued 6.6 ± 1.5 hours prior to surgical incision. In 55% of patients, cangrelor was resumed at 9 ± 6 hours following surgery for a mean of 39 ± 38 hours. One cardiac death was reported after 3 hours of cangrelor discontinuation prior to surgery. No ischemic outcomes occurred after surgery and up to 30-days follow-up. The mean hemoglobin drop was Conclusion Perioperative bridging therapy with cangrelor is a feasible approach for stented patients at high thrombotic risk and referred to surgery requiring DAPT discontinuation. Larger studies are warranted to support the safety of this strategy.

Differential diagnosis of shock occurring within few hours to percutaneous coronary intervention (PCI) performed to treat acute ST-segment elevation myocardial infarction (STEMI) encompass periprocedural complications and causes of other type, including adrenal crisis (AC), sometimes presenting as Takotsubo syndrome.

There is uncertainty in cardiologists’ attitudes for prolonging dual antiplatelet therapy (DAPT) with ticagrelor 60 mg beyond 12 months in post-myocardial infarction (MI) patients. We aimed at characterizing the Italian cardiologists’ perceptions and needs in the management of such patients. Two consecutive questionnaires were proposed between June and November 2021, and compiled by 122 and 87 Cardiologists, respectively. Agreement among cardiologists was defined as either a >70% frequency of concordant responses relative to total respondents or following the Delphi method as developed by the RAND Corporation. An agreement was reached on the indication of ticagrelor as the first choice P2Y12 inhibitor in MI patients, irrespective of the presentation [ST elevation MI (STEMI), 72%, vs. non-ST elevation MI (NSTEMI), 71%] or the management [invasive vs. conservative (75%)]. A consensus was also achieved on the possibility to consider a patient suitable for long-term DAPT with ticagrelor 60 mg even in case of another P2Y12 inhibitor used in the first year after the acute event (74, 85%). To define ischemic and bleeding risks, a consensus was reached on the utilization of one or more scores (87, 71%).

PURPOSE: Patients suffering from an acute coronary syndrome are at very high risk for recurrent events. Early targeted pharmacological intervention primarily aimed at controlling plasma LDL-cholesterol (LDL-C) levels can result in the reduction of recurrent cardiovascular events. This study aimed to evaluate real-life evidence from the Italian setting to document current practice of secondary prevention in patients after acute coronary syndrome (ACS), specifically assessing: (i) the rate of LDL-C target (

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists (ANMCO), reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure. Data deriving from a national survey in Italian hospitals about IABP use are also provided.

Coronary bifurcations exhibit localized turbulent flow and enhanced propensity for platelet deposition, plaque rupture, and atherothrombosis. Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with an increased risk of thrombotic events. Such risk is modulated by anatomical complexity, intraprocedural factors and pharmacological therapy. There is no consensus on the appropriate PCI strategy or the optimal regimen and duration of antithrombotic treatment in order to decrease the risk of ischemic and bleeding complications in the setting of coronary bifurcation. A uniform therapeutic approach meets a clinical need. The present initiative, promoted by the European Bifurcation Club (EBC), involves opinion leaders from Europe, America, and Asia with the aim to analyze the currently available evidence. Although mainly derived from sub-studies of large trials or small studies, or from authors' opinions, an algorithm for the optimal management of patients undergoing bifurcation PCI, developed on the basis of clinical presentation, bleeding risk, and intraprocedural strategy is here proposed.

Funding Acknowledgements Type of funding sources: None. Background Non-invasive ventilation (NIV) is an established treatment for acute decompensated heart failure (ADHF). Purpose The aim of the present analysis was to evaluate the feasibility of continuous positive airway pressure (CPAP) in patients with myocardial infarction (MI) and ADHF, during percutaneous coronary intervention (PCI). Methods Consecutive patients admitted for MI, receiving CPAP for ADHF in the cath lab during PCI were retrospectively included. The main study outcome was the feasibility of CPAP, intended as well tolerated by the patient and exclusive cardiology staff management. Results Between December 2018 and October 2020, 15 patients were included; median age was 79 (40-87 IQR) years, 8 (53%) were males, 9 (60%) presented with STEMI and 10 (67%) in cardiogenic shock. At admission median ejection fraction was 35 (20-60 IQR) % and 6 (40%) patients had severe mitral regurgitation. Mean PaO2/ FiO2 was 188.1 ± 74.9 mmHg/%, mean lactate level was 2.6 ± 1.5 mmol/L and NTproBNP 7882 (3139-35000 IQR) ng/L. The CPAP was set with a median FiO2 of 50 (35-80 IQR) % with a PEEP of 7.5 (5-10 IQR) mmHg. CPAP was feasible in 14 (93%) patients, as in only one case it was interrupted for patient’s intolerance. CPAP was always managed by nurses of the cath lab, without the support of anesthetist. One patient suffered cardiac arrest that led to CPAP interruption for resuscitation maneuvers. No patients underwent intubation in the cath lab. Post-procedural PaO2/FiO2 ratio substantially improved to 259.4 ± 96.9 mmHg/% (p = 0.03) and lactate decreased to 1.5 ± 0.5 mmol/L (p = 0.01, 42% median reduction). One patient died in-hospital due to underlying disease, unrelated to study procedure. Conclusion CPAP during PCI in patients with MI and ADHF was feasible, well tolerated and easily manageable. Larger studies are warranted to confirm these results.

The combination of oral anticoagulants (OAC) and dual antiplatelet therapy (DAPT) is the mainstay for the treatment of patients with atrial fibrillation (AF) presenting with acute coronary syndrome (ACS) and/or undergoing PCI. However, this treatment leads to a significant increase in risk of bleeding. In most cases, according to the most recent guidelines, triple antithrombotic therapy (TAT) consisting of OAC and DAPT, typically aspirin and clopidogrel, should be limited to one week after ACS and/or PCI (default strategy). On the other hand, in patients with a high ischemic risk (i.e., stent thrombosis) and without increased risk of bleeding, TAT should be continued for up to one month. Direct oral anticoagulants (DOAC) in triple or dual antithrombotic therapy (OAC and P2Y12 inhibitor) should be favored over vitamin K antagonists (VKA) because of their favorable risk/benefit profile. The choice of the duration of TAT (one week or one month) depends on a case-by-case evaluation of a whole series of hemorrhagic or ischemic risk factors for each patient. Likewise, the specific DOAC treatment should be selected according to the clinical characteristics of each patient. We propose a series of paradigmatic clinical cases to illustrate the decision-making work-up in clinical practice.

Polycystic ovarian syndrome (PCOS) has an overall negative impact on quality of life (QoL). Various signs and symptoms of PCOS have variable influence on QoL likely because of socio-cultural issues. Among these symptoms, dermatological issues (hirsutism, acne, alopecia) and overweight/obesity are associated with low self-esteem and poor body image, whereas menstrual irregularities determine distress and concerns about fertility, being infertility itself a major contributor to reduced QoL. Moreover, PCOS is associated to a higher risk of anxiety and depression and with body image distress and other psychiatric disorders. That being, psychological and emotional components should be routinely screened and treated in PCOS women. The impact of PCOS on sexual function is controversial, given the multifactorial causes of women’s sexual dysfunction and the different phenotypes and severity of PCOS. Being as it may, while biochemical hyperandrogenemia of PCOS might act as a protective factor on sexual function, clinical signs of hyperandrogenism, which reflect individual androgen sensitivity, may be a cause of sexual dysfunction through impaired body image.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, either symptomatic or incidental, is a common complication in the history of cancer disease. The risk of VTE is 4-7-fold higher in oncology patients, and it represents the second leading cause of death, after cancer itself. In cancer patients, compared with the general population, VTE therapy is associated with higher rates of recurrent thrombosis and/or major bleeding. The need for treatment of VTE in patients with cancer is a challenge for the clinician because of the multiplicity of types of cancer, the disease stage and the imbricated cancer treatment. Historically, in cancer patients, low molecular weight heparins have been preferred for treatment of VTE. More recently, in large randomized clinical trials, direct oral anticoagulants (DOACs) demonstrated to reduce the risk of VTE. However, in the "real life", uncertainties remain on the use of DOACs, especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-to-drug interactions with specific anticancer therapies.In cancer patients, atrial fibrillation can arise as a perioperative complication or for the side effect of some chemotherapy agents, as well as a consequence of some associated risk factors, including cancer itself. The current clinical scores for predicting thrombotic events (CHA2DS2-VASc) or for predicting bleeding (HAS-BLED), used to guide antithrombotic therapy in the general population, have not yet been validated in cancer patients. Encouraging data for DOAC prescription in patients with atrial fibrillation and cancer are emerging: recent post-hoc analysis showed safety and efficacy of DOACs for the prevention of embolic events compared to warfarin in cancer patients. Currently, anticoagulant therapy of cancer patients should be individualized with multidisciplinary follow-up and frequent reassessment. This consensus document represents an advanced state of the art on the subject and provides useful notes on clinical practice.

Recreational drug use may cause coronary artery disease through several mechanisms. An increasing number of young patients with drug-related acute coronary syndrome have been reported over recent years. The present position statement reports the most recent epidemiological data on acute coronary syndrome in the setting of drug abuse, describes the main pathophysiological mechanisms underlying coronary artery disease and acute events in these patients, and provides practical recommendations on management and an overview of prognosis.

Although oral P2YThe purpose of this study was to compare downstream and upstream oral P2YWe performed a randomized, adaptive, open-label, multicenter clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was the superiority of the downstream versus the upstream strategy on the combination of efficacy and safety events (net clinical benefit).We randomized 1,449 patients to downstream or upstream oral P2YDownstream and upstream oral P2Y

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like traditional anticoagulants, novel oral anticoagulants may cause gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of gastrointestinal bleeding as compared with warfarin. However, the usefulness of PPIs in patients receiving these anticoagulants deserves to be further demonstrated. Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

The aim of this study was to assess long-term drug adherence and prognosis in real-world patients discharged on dual-antiplatelet therapy (DAPT) after acute myocardial infarction (AMI). A retrospective cohort analysis using administrative databases kept by eight local health units was performed. DAPT exposure (defined as ≥ 2 prescriptions), adherence, and the occurrence of major adverse events (MACE) were analyzed during a 36-month follow-up. The analysis included 11,101 patients who were discharged alive with a primary diagnosis of AMI. Of these, 5,919 patients (53.31%) were discharged on DAPT without a diagnosis of cancer or anemia, without transient DAPT discontinuation, and represented the study population. DAPT discontinuation occurred in 2,200 patients (37.2%) and in 1,995 (33.7%) after the first 6 and 12 months, respectively, whereas 423 patients (7.1%) were still on DAPT after 36 months. Patients who maintained DAPT up to 12 months had a significantly lower overall mortality, compared with patients who discontinued DAPT after 6 months. Exposure to DAPT at 3 years was associated with reduced all-cause mortality (hazard ratio [HR]: 0.067, 95% confidence interval [CI]: 0.027–0.162, p

Luca Degli Esposti,1 Valentina Perrone,1 Chiara Veronesi,1 Stefano Buda,1 Roberta Rossini2 On behalf of the Local Health Unit group 1Clicon S.r.l. Health, Economics & Outcomes Research, Ravenna, Italy; 2Department of Cardiology, Papa Giovanni XXIII Hospital, Bergamo, Italy Objectives: The aim of the study was to assess all-cause mortality and cardiovascular (CV) events in patients after a period of 12 months of treatment with dual antiplatelet therapy (DAPT) after hospitalization for acute myocardial infarction (AMI) in a real-world setting. Health care costs for the management of patients post-AMI was also assessed. Methods: A retrospective analysis using data from the administrative databases of six local health units (LHUs) was performed. All beneficiaries of these LHUs hospitalized with AMI between January 01, 2010, and December 31, 2011, and exposed to a treatment period with DAPT up to 12 months after AMI discharge were included. All-cause mortality, CV hospitalizations, and health care costs occurring during the 36-month follow-up period from end of treatment with DAPT were considered. For the cost analysis, only patients still alive at the end of the follow-up period were included. Results: A total of 2,721 patients were included (mean ± SD age 63.6±17.3 years, 67.8% males). About 17% and 18% of all patients had CV events and died during the follow-up period, respectively. The annual mean cost per patient was €3,523.27. During the follow-up period, 63 patients had a second AMI event; for whom, the mean health care cost per patient was €19,570.70. Conclusion: In a real-world setting in Italy, considering a 36-month follow-up period, all-cause mortality, CV events, and related health care cost of patients hospitalized with an AMI undergoing a 12-month treatment period with DAPT remained relevant. This study suggests that increased efforts aimed at the prevention of recurrent AMI are warranted, as well as an accurate risk stratification in order to improve long-term outcome. Keywords: dual platelet aggregation inhibition, acute myocardial infarction, real-world setting

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. Results: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01777503.

Background Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel. Aim The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals. Patients and methods A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization. Results At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription. Conclusion In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher thrombotic risk, did not influence this choice; however, bleeding risk was taken into account.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

Perioperative management of antithrombotic therapy in patients treated with coronary stents undergoing surgery remains poorly defined. Importantly, surgery represents a common reason for premature treatment discontinuation, which is associated with an increased risk in mortality and major adverse cardiac events. However, maintaining antithrombotic therapy to minimize the incidence of perioperative ischemic complications may increase the risk of bleeding complications. Although guidelines provide some recommendations with respect to the perioperative management of antithrombotic therapy, these have been largely developed according to the thrombotic risk of the patient and a definition of the hemorrhagic risk specific to each surgical procedure, key to defining the trade-off between ischemia and bleeding, is not provided. These observations underscore the need for a multidisciplinary collaboration among cardiologists, anesthesiologists, hematologists and surgeons to reach this goal. The present document is an update on practical recommendations for standardizing management of antithrombotic therapy management in patients treated with coronary stents (Surgery After Stenting 2) in various types of surgery according to the predicted individual risk of thrombotic complications against the anticipated risk of surgical bleeding complications. Cardiologists defined the thrombotic risk using a "combined ischemic risk" approach, while surgeons classified surgeries according to their inherent hemorrhagic risk. Finally, a multidisciplinary agreement on the most appropriate antithrombotic treatment regimen in the perioperative phase was reached for each surgical procedure.